Adcy6, short for adenylate cyclase 6, is a member of the membrane-bound adenylate cyclase family. It converts adenosine triphosphate (ATP) into cAMP and pyrophosphate. cAMP is a key second-messenger involved in multiple cellular signaling pathways, such as the glucagon/ADCY6/cAMP/PKA/CREB signaling pathway which helps maintain glucose homeostasis [2]. It is also associated with the Hippo signaling pathway and the β-adrenergic receptor-related pathways, playing important roles in various biological processes and diseases [1,4].

In oral tongue squamous cell carcinoma (OTSCC), lower ADCY6 expression indicates a poorer prognosis, and forced expression of ADCY6 can inhibit cell proliferation, migration, invasion, and promote apoptosis, likely by impairing the Hippo signaling pathway [1]. In breast cancer, ADCY6 is expressed at low levels, and its low expression is related to the methylation state regulated by TET1, affecting the epithelial-mesenchymal transition (EMT) process [3]. In arthrogryposis multiplex congenita, a homozygous missense mutation in ADCY6 was found in a family, indicating its role in peripheral nervous system myelination likely through the cAMP pathway [5]. In B-cell acute lymphoblastic leukemia, knockdown of GPSM1 inhibits cell proliferation and promotes apoptosis by suppressing the ADCY6-RAPGEF3-JNK signaling pathway [6].

In summary, Adcy6 is crucial for multiple biological processes and is involved in various diseases. Its role in diseases like OTSCC, breast cancer, arthrogryposis multiplex congenita, and B-cell acute lymphoblastic leukemia has been revealed through different research models. These findings contribute to understanding the disease mechanisms and may provide potential therapeutic targets.

References:

1. Yang, Sen, Guo, Li-Juan, Liang, Yong, Luo, Jia, Mu, Yan-Dong. 2023. ADCY6 is a potential prognostic biomarker and suppresses OTSCC progression via Hippo signaling pathway. In The Kaohsiung journal of medical sciences, 39, 978-988. doi:10.1002/kjm2.12725. https://pubmed.ncbi.nlm.nih.gov/37574908/

2. Jia, Linna, Jiang, Yunfeng, Li, Xinzhi, Chen, Zheng. 2019. Purβ promotes hepatic glucose production by increasing Adcy6 transcription. In Molecular metabolism, 31, 85-97. doi:10.1016/j.molmet.2019.11.008. https://pubmed.ncbi.nlm.nih.gov/31918924/

3. Wu, Hao, Qiu, Juanjuan, Wu, Zhenru, Zhou, Chen, Lv, Qing. 2022. MiR-27a-3p binds to TET1 mediated DNA demethylation of ADCY6 regulates breast cancer progression via epithelial-mesenchymal transition. In Frontiers in oncology, 12, 957511. doi:10.3389/fonc.2022.957511. https://pubmed.ncbi.nlm.nih.gov/35978806/

4. Deng, Yunfei, Wang, Jun, Xie, Guojin, Zeng, Xiaochen, Li, Hongli. 2019. Circ-HIPK3 Strengthens the Effects of Adrenaline in Heart Failure by MiR-17-3p - ADCY6 Axis. In International journal of biological sciences, 15, 2484-2496. doi:10.7150/ijbs.36149. https://pubmed.ncbi.nlm.nih.gov/31595165/

5. Laquérriere, Annie, Maluenda, Jérome, Camus, Adrien, Tawk, Marcel, Melki, Judith. 2013. Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects. In Human molecular genetics, 23, 2279-89. doi:10.1093/hmg/ddt618. https://pubmed.ncbi.nlm.nih.gov/24319099/

6. Zhang, Ye, Zhou, Bo, Sun, Jingjing, He, Qun, Zhao, Yujie. 2021. Knockdown of GPSM1 Inhibits the Proliferation and Promotes the Apoptosis of B-Cell Acute Lymphoblastic Leukemia Cells by Suppressing the ADCY6-RAPGEF3-JNK Signaling Pathway. In Pathology oncology research : POR, 27, 643376. doi:10.3389/pore.2021.643376. https://pubmed.ncbi.nlm.nih.gov/34257610/